This project proposes to investigate protein-protein interactions of HIV integrase with host protein. In previous studies, the PI used the yeast two hybrid system to isolate mutants of HIV integrase defective in oligomerization. She has also used the two hybrid system to identify a protein, Ini-1, that binds tightly to HIV-1 integrase. Ini-1 turns out to be similar in sequence to Snf-5, a component of the Swi/Snf complex proposed to be involved in gene activation. The PI plans to investigate heteromeric protein-protein interactions by further experiments using the yeast two hybrid system. Mutants will be generated that influence these interactions, and their phenotypes studied in vitro and in vivo. The influences of Ini-1 on target site selection during retroviral integration will also be investigated, as will the role of Ini-1 in the HIV life cycle. It is hoped that results of these studies will be useful in devising integration inhibitors and in developing new gene therapy methods.